Microencapsulation of viral or bacterial antigens has been found to enhance antigen-specific immune responses in experimental animals. The promise of these findings has encouraged studies of microencapsulated antigens in adult volunteers. However, little is known about the mechanisms by which microencapsulation enhances the immune response, the capacity of microencapsulation to induce an immune response which protects against challenge, or the potential for microencapsulation to perturb antigen-specific immune responses. For example, micro- encapsulated viruses inoculated orally may bypass antigen presentation by mucosal epithelial cells, select for antigen uptake by macrophages, and protect virus from exposure to mucosal proteases. These changes may perturb the balance between virus-specific humoral and cellular immune responseS or alter the proteins recognized by virus-specific antibodies or cytotoxic T lymphocytes (CTLs). We recently developed a system of microencapsulation using aqueous anionic polymers and aqueous amines (charged-film microcapsules). The capacity of water-soluble reagents to encapsulate infectious virus obviates concerns about loss of antigenicity associated with organic solvent-based systems of microencapsulation. Using the intestinal pathogen, rotavirus, we found that charged-film microcapsules have the capacity to enhance rotavirus immunogenicity after oral inoculation of mice. We will extend these observations by addressing the following questions: 1) What are the mechanisms by which microencapsulation of virus enhances virus-specific immunity? 2) Does oral inoculation of mice with microencapsulated preparations of rotavirus or rotavirus proteins alter the magnitude of or balance between virus-specific humoral and cellular responses? 3) Does microencapsulation of rotavirus alter the fine antigenic specificities of virus-specific neutralizing antibodies or CTLs? 4) Does oral inoculation of mice with microencapsulated virus or viral proteins enhance the capacity of immunization to protect against challenge?